An annular corneal microneedle patch for minimally invasive ophthalmic drug delivery
Lu Wang, Yishun Guo, Ben Chen, Si Lu, Jianhua Yang, Yingying Jin, Xinyi Wang, Xinyue Sun, Shuting Wang, Bailiang Wang
Abstract
Microneedles directly penetrating into the cornea inevitably cause pain, corneal structure damage, and reduced light transmittance. In this work, a minimally invasive annular microneedle (A-MN) patch was developed avoiding direct puncture into the central cornea for ophthalmic drug delivery. The feasible mechanical strength of A-MNs was achieved by adjusting the ratio of PVP-β-CD and PVA to puncture the cornea barrier. Through effective diffusion to corneal stroma, bioavailability of hydrophilic small-molecule drugs, hydrophobic drugs, and macromolecular protein drugs through an A-MN patch was 24.36, 17.47, and 5.36 times higher than that of free drug administration. A-MNs effectively maintained light transmittance of the cornea with a light transmittance of 96.33 to 100%, which was higher than that of S-MNs. Furthermore, A-MNs effectively avoided corneal tissue and nerve damage along with the pain. The efficiency and safety of A-MNs were also examined through both an in vitro cell experiment and an in vivo animal experimental model, which showed great potential in clinical application.